Dipeptidyl peptidase IV (hereinafter also referred to as DPPIV) is a cell membrane protein, which has been found in epithelial cell of small intestine, prostate gland, renal tubule, biliary tract and the like, activated T-cell, B-cell, NK-cell and the like. In the DPPIV, deduced active sites of DPPIV in the C-terminal side are located in extracellular portions and those in the N-terminal side are located in cytoplasm in a living body. Also, there has been suggested the relationship of the above-mentioned DPPIV with the activities of various cytokines such as interleukin-1β, interleukin-2, interleukin-3, interleukin-5, interleukin-6, interleukin-13, tumor necrosis factory and the like, and activities of various chemokines such as RANTES and the like in immune system [Rinsho Menneki (Clinical Immunology), 34, Revised and Enlarged Edition 19, 45-53, published by Kagaku Hyoronsha (2000), and the like].
As to the dipeptidyl peptidase IV, it has been shown that some amino acid residues can be involved in exhibition of the activity of the dipeptidyl peptidase IV by experiments such as biochemical experiments using inhibitors, experiments using mutants produced by site-directed mutagenesis [for example, see Misumi et al, Biochim. Biophys. Acta, 1131, 333-336 (1992), Ogata et al, Biochemistry, 31, 2582-2587 (1992) and the like].
However, it is difficult to know the three-dimensional structures for active sites from the information. Therefore, it is presently difficult to obtain the three-dimensional structural information for identifying, searching, evaluating or designing an interaction of the dipeptidyl peptidase IV and a compound that acts with the dipeptidyl peptidase IV on the level of three-dimensional structure and a novel compound capable of binding with and acting on the dipeptidyl peptidase IV.